Insulin resistance and exercise tolerance in heart failure patients: linkage to coronary flow reserve and peripheral vascular function

TY - JOUR

T1 - Insulin resistance and exercise tolerance in heart failure patients

T2 - linkage to coronary flow reserve and peripheral vascular function

AU - Snoer, Martin

AU - Monk-Hansen, Tea

AU - Olsen, Rasmus Huan

AU - Pedersen, Lene Rørholm

AU - Simonsen, Lene

AU - Rasmusen, Hanne

AU - Dela, Flemming

AU - Prescott, Eva

PY - 2012/8/13

Y1 - 2012/8/13

N2 - Background: Insulin resistance has been linked to exercise intolerance in heart failure patients. The aim of this study was to assess the potential role of coronary flow reserve (CFR), endothelial function and arterial stiffness in explaining this linkage.Methods: 39 patients with LVEF < 35% (median LV ejection fraction (LVEF) 31 (interquartile range (IQ) 26-34), 23/39 of ischemic origin) underwent echocardiography with measurement of CFR. Peak coronary flow velocity (CFV) was measured in the LAD and coronary flow reserve was calculated as the ratio between CFV at rest and during a 2 minutes adenosine infusion. All patients performed a maximal symptom limited exercise test with measurement of peak oxygen uptake (VO2peak), digital measurement of endothelial function and arterial stiffness (augmentation index), dual X-ray absorptiometry scan (DEXA) for body composition and insulin sensitivity by a 2 hr hyperinsulinemic (40 mU/min/m2) isoglycemic clamp.Results: Fat free mass adjusted insulin sensitivity was significantly correlated to VO2peak (r = 0.43, p = 0.007). Median CFR was 1.77 (IQ 1.26-2.42) and was correlated to insulin sensitivity (r 0.43, p = 0.008). CFR (r = 0.48, p = 0.002), and arterial stiffness (r = -0.35, p = 0.04) were correlated to VO2peak whereas endothelial function and LVEF were not (all p > 0.15). In multivariable linear regression adjusting for age, CFR remained independently associated with VO2peak (standardized coefficient (SC) 1.98, p = 0.05) whereas insulin sensitivity (SC 1.75, p = 0.09) and arterial stiffness (SC -1.17, p = 0.29) were no longer associated with VO2peak.Conclusions: The study confirms that insulin resistance is associated with exercise intolerance in heart failure patients and suggests that this is partly through reduced CFR. This is the first study to our knowledge that shows an association between CFR and exercise capacity in heart failure patients and links the relationship between insulin resistance and exercise capacity to CFR.

AB - Background: Insulin resistance has been linked to exercise intolerance in heart failure patients. The aim of this study was to assess the potential role of coronary flow reserve (CFR), endothelial function and arterial stiffness in explaining this linkage.Methods: 39 patients with LVEF < 35% (median LV ejection fraction (LVEF) 31 (interquartile range (IQ) 26-34), 23/39 of ischemic origin) underwent echocardiography with measurement of CFR. Peak coronary flow velocity (CFV) was measured in the LAD and coronary flow reserve was calculated as the ratio between CFV at rest and during a 2 minutes adenosine infusion. All patients performed a maximal symptom limited exercise test with measurement of peak oxygen uptake (VO2peak), digital measurement of endothelial function and arterial stiffness (augmentation index), dual X-ray absorptiometry scan (DEXA) for body composition and insulin sensitivity by a 2 hr hyperinsulinemic (40 mU/min/m2) isoglycemic clamp.Results: Fat free mass adjusted insulin sensitivity was significantly correlated to VO2peak (r = 0.43, p = 0.007). Median CFR was 1.77 (IQ 1.26-2.42) and was correlated to insulin sensitivity (r 0.43, p = 0.008). CFR (r = 0.48, p = 0.002), and arterial stiffness (r = -0.35, p = 0.04) were correlated to VO2peak whereas endothelial function and LVEF were not (all p > 0.15). In multivariable linear regression adjusting for age, CFR remained independently associated with VO2peak (standardized coefficient (SC) 1.98, p = 0.05) whereas insulin sensitivity (SC 1.75, p = 0.09) and arterial stiffness (SC -1.17, p = 0.29) were no longer associated with VO2peak.Conclusions: The study confirms that insulin resistance is associated with exercise intolerance in heart failure patients and suggests that this is partly through reduced CFR. This is the first study to our knowledge that shows an association between CFR and exercise capacity in heart failure patients and links the relationship between insulin resistance and exercise capacity to CFR.

KW - Absorptiometry, Photon

KW - Aged

KW - Biological Markers

KW - Blood Glucose

KW - Chi-Square Distribution

KW - Denmark

KW - Endothelium, Vascular

KW - Exercise Test

KW - Exercise Therapy

KW - Exercise Tolerance

KW - Female

KW - Fractional Flow Reserve, Myocardial

KW - Glucose Clamp Technique

KW - Heart Failure

KW - Humans

KW - Insulin

KW - Insulin Resistance

KW - Linear Models

KW - Male

KW - Middle Aged

KW - Multivariate Analysis

KW - Predictive Value of Tests

KW - Pulse Wave Analysis

KW - Risk Assessment

KW - Risk Factors

KW - Stroke Volume

KW - Vascular Stiffness

KW - Ventricular Function, Left

U2 - 10.1186/1475-2840-11-97

DO - 10.1186/1475-2840-11-97

M3 - Journal article

C2 - 22889317

SN - 1475-2840

VL - 11

SP - 97

JO - Cardiovascular Diabetology

JF - Cardiovascular Diabetology

ER -